785O - PIVOT IO 001: First disclosure of efficacy and safety of bempegaldesleukin (BEMPEG) plus nivolumab (NIVO) vs NIVO monotherapy in advanced melanoma (MEL)

Background

BEMPEG, an IL-2 prodrug, combined with NIVO, a PD-1 inhibitor, showed clinical activity with a manageable safety profile in patients (pts) with advanced MEL in the phase 1/2 PIVOT-02 study. These data supported initiation of the phase 3, randomized, open-label PIVOT IO 001 study (NCT03635983) evaluating BEMPEG + NIVO vs NIVO in advanced MEL. Here we report efficacy and safety of PIVOT IO 001.

Methods

Pts with previously untreated, unresectable or metastatic MEL were randomized 1:1 to receive BEMPEG 0.006 mg/kg IV + NIVO 360 mg IV Q3W or NIVO 360 mg IV Q3W, stratified by PD-L1 tumor cell expression, BRAF mutation status, and AJCC v8 M stage. Primary endpoints were objective response rate (ORR) and progression-free survival (PFS), both by blinded independent central review per RECIST v1.1, and overall survival (OS). Overall study α was 0.05, split with 0.001 for ORR, 0.03 for PFS, and 0.019 for OS. All α are 2-sided.

Results

783 pts were randomized to BEMPEG + NIVO (n = 391) or NIVO (n = 392); baseline characteristics were balanced across arms. Median follow-up was 19.3 months (mo) and 11.6 mo for ORR and PFS, respectively. The ORR with BEMPEG + NIVO was 27.7% vs 36.0% with NIVO (2-sided P = 0.0311). Disease control rate was 56.1% with BEMPEG+ NIVO and 58.5% with NIVO. Median PFS with BEMPEG + NIVO was 4.17 mo (95% CI, 3.52–5.55) vs 4.99 mo (4.14–7.82) with NIVO; HR, 1.09 (97% CI, 0.88–1.35); P = 0.3988. Median OS was 29.67 mo (95% CI, 22.14–not reached [NR]) for BEMPEG + NIVO vs 28.88 mo (21.32–NR) with NIVO (HR, 0.94; 99.93% CI, 0.59–1.48; P = 0.6361). Grade 3–4 drug-related adverse events (AEs) and serious AEs were higher with BEMPEG + NIVO (21.7% and 10.1%) vs NIVO (11.5% and 5.5%). An AE of special interest, ischemic cerebrovascular events, was higher with BEMPEG + NIVO (2.6%) vs NIVO (0.8%). There were 3 BEMPEG + NIVO and 1 NIVO treatment-related deaths.

Conclusions

In pts with advanced MEL, BEMPEG + NIVO demonstrated no added clinical efficacy vs NIVO. Primary endpoints ORR, PFS, and OS did not meet the prespecified boundary for statistical significance. Increased toxicity was observed with BEMPEG + NIVO vs NIVO. Ongoing biomarker analysis may help further interpret study results.

Clinical trial identification

NCT03635983.

Editorial acknowledgement

Editorial assistance was provided by Sara Thier and Michele Salernitano from Ashfield MedComms.

Legal entity responsible for the study

Bristol Myers Squibb.

Funding

Bristol Myers Squibb.

Disclosure

A. Diab: Financial Interests, Personal, Advisory Board: Nektar Therpaeutics, Apexigen, Idera Pharmaceuticals. H.J. Gogas: Financial Interests, Personal, Advisory Board: MSD, BMS, Pierre Fabre; Financial Interests, Personal, Invited Speaker: MSD, BMS, Novartis, Pierre Fabre, Sanofi; Financial Interests, Invited Speaker: Amgen, Replimune; Financial Interests, Institutional, Invited Speaker: Amgen, MSD, BMS, Replimune, Iovance; Financial Interests, Institutional, Research Grant: BMS, Pfizer. S.K. Sandhu: Financial Interests, Institutional, Advisory Board, I have served on advisory boards for BMS. The contracts for my role are set up with the institution and the funds go to a research fund at Peter MacCallum Cancer Centre: Bristol Myers Squib; Financial Interests, Institutional, Advisory Board, I have served on advisory boards for MSD. The contracts for my role are set up with the institution and the funds go to a research fund at Peter MacCallum Cancer Centre: Merck Sharp and Dohme; Financial Interests, Institutional, Advisory Board, I have served on advisory boards for AstraZeneca. The contracts for my role as an advisor are set up with the institution and the funds go to a research fund at Peter MacCallum Cancer Centre: AstraZeneca; Financial Interests, Institutional, Advisory Board, I have served on advisory boards for Novartis. The contracts for my role as an advisor are set up with the institution and the funds go to a research fund at Peter MacCallum Cancer Centre: Novartis; Financial Interests, Institutional, Advisory Board, I have served on an advisory board for Merck Serono. The contracts for my service are set up with the institution and funds go into a research fund at the Peter MacCallum Cancer Centre: Merck Serono; Financial Interests, Institutional, Research Grant, My institution receives grant funding to run an investigator initiated trial that I lead: Novartis, Genentech, Amgen, AstraZeneca, Merck Serono, Merck Sharp and Dohme; Non-Financial Interests, Principal Investigator, I am a principal investigator on several of Janssen sponsored studies and don't receive any renumeration for this: Janssen; Non-Financial Interests, Principal Investigator, I am a principal investigator on several Novartis sponsored studies and don’t receive any renumeration for this: Novartis; Non-Financial Interests, Principal Investigator, I am a principal investigator on several of Genentech sponsored studies and don't receive any renumeration for this: Genentech; Non-Financial Interests, Principal Investigator, I am a principal investigator on several of Bristol Myers Squibb sponsored studies and don't receive any renumeration for this: Bristol Myers Squibb; Non-Financial Interests, Other, I serve on the Independent Safety and Data Monitoring committee for 2 of Novartis sponsored studies and don’t receive any compensation for this: Novartis; Non-Financial Interests, Principal Investigator, I am the Principal Investigator for several AstraZeneca sponsored studies and am not remunerated for this: AstraZeneca; Non-Financial Interests, Other, I serve on the steering committee for several Janssen sponsored trials and I do not receive compensation for this: Janssen; Non-Financial Interests, Other, I serve on the steering committee for one AstraZeneca sponsored trial and I do not receive compensation for this: AstraZeneca; Non-Financial Interests, Other, I serve on the steering committee for one Genentech sponsored trials and I do not receive compensation for this: Genentech; Non-Financial Interests, Other, I serve on the steering committee for a Bristol Myers Squibb sponsored trial and I do not receive renumeration for this: Bristol Myers Squibb. G.V. Long: Financial Interests, Personal, Other, Consultant Advisor: Agenus Inc, Amgen Inc, Array Biopharma Inc, Boehringer Ingelheim International GmbH, Bristol Myers Squibb, Evaxion Biotech A/S, Hexal AG (Sandoz Company), Merck Sharpe & Dohme (Australia) Pty Limited, Novartis Pharma AG, OncoSec Medical Australia, Pierre Fabre, Provectus Australia, Qbiotics Group Limited, Regeneron Pharmaceuticals Inc; Financial Interests, Personal, Advisory Board, Consultant Advisor: Highlight Therapeutics S.L. P.A. Ascierto: Financial Interests, Personal, Other, Consultant and Advisory Role: BMS, Roche Genentech, MSD, Novartis, Pfizer/Array, Merck Serono, Pierre Fabre, AstraZeneca, Sun Pharma, Sanofi, Idera, Sandoz, Immunocore, 4SC, Nektar, Boehringer Ingelheim, Regeneron; Financial Interests, Personal, Other, Consultant Role: Italfarmaco; Financial Interests, Personal, Other, Advisory Role: Eisai, Seagen; Financial Interests, Personal, Other, Consultant Role: Daiichi Sankyo, Pfizer, Oncosec, Nouscom, Lunaphore; Financial Interests, Personal, Other, Consultant role: Medicenna, Bio-AI Health; Financial Interests, Institutional, Funding, Clinical trial and translational research: BMS; Financial Interests, Institutional, Funding, Clinical Trial: Roche Genentech, Pfizer/Array, Sanofi; Non-Financial Interests, Leadership Role, President since 2010: Fondazione Melanoma Onlus Italy; Non-Financial Interests, Leadership Role, President since 2014: Campania Society of ImmunoTherapy of Cancer (SCITO) Italy; Non-Financial Interests, Other, Member of Steering Committee since 2016: Society for Melanoma Research (SMR); Non-Financial Interests, Invited Speaker, November 2017 - December 2021: Society for Immunotherapy of Cancer (SITC); Non-Financial Interests, Member: ASCO, SITC, EORTC Melanoma Cooperative Group, AIOM, SMR; Other, Travel Support: MSD. J. Larkin: Financial Interests, Personal, Invited Speaker: BMS, Pfizer, Roche, Pierre Fabre, AstraZeneca, Novartis, EUSA Pharma, MSD, Merck, GSK, Ipsen, Aptitude, Eisai, Calithera, Ultimovacs, Seagen, Goldman Sachs, eCancer, Inselgruppe, Agence Unik; Financial Interests, Personal, Other, Consultancy: Incyte, iOnctura, Apple Tree, Merck, BMS, Eisai, Debipharm; Financial Interests, Personal, Other, Honorarium: touchIME, touchEXPERTS, VJOncology, RGCP, Cambridge Healthcare Research, Royal College of Physicians; Financial Interests, Institutional, Funding: BMS, MSD, Novartis, Pfizer, Achilles, Roche, Nektar, Covance, Immunocore, Pharmacyclics, Aveo. M. Sznol: Financial Interests, Personal, Other, Consulting fees: Biond, Adaptimmune, Bristol-Myers, Biontech, Simcha, Verastem, Pfizer, Innate pharma, PIO Therapeutics, Kadmon – Sanofi, Pierre-Fabre, Incyte, Alligator, Ocellaris-Lilly, Numab, Immunocore, Adagene, Kanaph, iTEOS, Genocea, Sapience, Targovax, Molecular Pa; Financial Interests, Personal, Stocks/Shares: Adaptive Biotechnologies, Amphivena, Intensity, Actym, Evolveimmune, Nextcure, Repertoire, Oncohost, Asher, Rootpath, Johnson and Johnson, GlaxoSmithKline; Financial Interests, Personal, Sponsor/Funding, Clinical Trial Sponsors: Vyread/Regeneron Roche Dragonfly Alpine . T. Ciuleanu: Financial Interests, Personal, Other, speaker, consultancy, advisory role: Roche, BMS, MSD, Pfizer, Eli Lilly, AstraZeneca, Sanofi, Sandoz, Novartis, Janssen, Astellas, Amgen. E. Muñoz Couselo: Financial Interests, Personal, Advisory Board: BMS, Novartis, Sanofi, Pierre Fabre, Sun Pharma, MSD; Financial Interests, Personal, Invited Speaker: Novartis, Roche, BMS, Sanofi, MSD, Pierre Fabre. C. Lebbe: Financial Interests, Personal, Speaker’s Bureau: Roche, Bristol Myers Squibb, Novartis, Amgen, MSD; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, MSD, Novartis, Amgen, Roche, Merck Serono, Sanofi, Pierre Fabre; Financial Interests, Personal, Other, Honoraria: Roche, Bristol Myers Squibb, Novartis, Amgen, MSD, Pierre Fabre, Pfizer, Incyte; Financial Interests, Personal, Member of the Board of Directors: Avantis Medical Systems ; Financial Interests, Personal, Funding, Research funding/money paid to my institution (PI, coordination, PI at national level): Roche, Bristol Myers Squibb, Novartis, MSD; Other, Personal, Other, Travel, accommodations, expenses: Bristol Myers Squibb, MSD, Novartis, Sanofi, Pierre Fabre. F. Meier: Financial Interests, Personal, Other, speaker, consultancy, advisory role: Novartis, Roche, BMS, MSD, Pierre Fabre, Sanofi; Financial Interests, Personal, Funding, Research funding (Investigator Initiated trial/Coordinating PI/Payment institutional): Roche. B. Curti: Financial Interests, Institutional, Funding, research funding to institution: Bristol Myers Squibb, Nektar. C. Rojas: Financial Interests, Personal, Other, speaker, consultancy, advisory role: Roche, BMS, MSD, AstraZeneca, Boeringher Ingelheim, Eli Lilly, Eisai, Merck Serono, Pfizer; Non-Financial Interests, Personal, Advisory Role: Roche, BMS, MSD, AstraZeneca, Boeringher Ingelheim, Eli Lilly, Eisai, Merck Serono, Pfizer. M. Zhou: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. S. Ravimohan: Financial Interests, Institutional, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. M.A. Tagliaferri: Financial Interests, Institutional, Full or part-time Employment, Senior Vice President: Nektar; Financial Interests, Institutional, Invited Speaker: Enzo Biochem, RayzeBio; Financial Interests, Institutional, Stocks/Shares: Nektar, Enzo Biochem, RayzeBio. N. Khushanlani: Financial Interests, Personal, Advisory Board: Bristol Myers-Squibb, Regeneron Pharmaceuticals, Merck, Iovance Biotherapeutics, Genzyme, Nektar, Castle Biosciences, Instil Bio, Novartis; Financial Interests, Personal, Other, Data Safety Monitoring Committee: Incyte, AstraZeneca; Financial Interests, Personal, Stocks/Shares: Amarin, Asensus Surgical, Bellicum; Financial Interests, Institutional, Invited Speaker: Bristol Myers-Squibb, Merck, Novartis, GlaxoSmithKline, HUYA, Regeneron, Celgene, Replimune; Financial Interests, Personal, Invited Speaker: Bristol Myers-Squibb, Regeneron, Nektar; Financial Interests, Invited Speaker: Replimune; Non-Financial Interests, Principal Investigator, Global clinical trial: HUYA. All other authors have declared no conflicts of interest.